Abstract: Imaging Core The Imaging Core of the Chronic HIV Infection, Aging and NeuroAIDS (CHAIN) Center consists of two laboratories, the Preclinical Imaging Laboratory (M. Boska, Co-PI) and the Human Structural and Functional Neuroimaging Laboratory (T. Wilson, Co-PI). The primary goals of the Core are to support CHAIN PIs and other neuroAIDS investigators in the identification and quantification of HIV-related alterations in brain function, structure, and metabolism, and to aid in understanding how emerging therapeutics modulate brain function to ameliorate and/or reverse these HIV-related alterations. Discovery of neural biomarkers of HIV-associated neurocognitive disorders (HAND) and the basic mechanisms of HIV-related brain injury remains a high priority, with 35-70% of all HIV-infected patients developing HAND in the post cART era. Surprisingly, despite this persistently high prevalence, there are currently no diagnostic tests or any specific biomarkers that can precisely pinpoint HAND, be used to monitor disease progression, or as an assay of an emerging treatment?s beneficial effects. The CHAIN Imaging Core has been designed for biomarker discovery and optimization, as the same imaging assessments can be performed in parallel in animal models and human trials. Such a parallel approach allows bidirectional feedback between animal and human studies, and will enhance abilities to diagnosis, monitor, and predict HAND in humans, while providing targets for detailed histological and biochemical studies of the underlying mechanisms. Alterations will be assessed with regard to age, viral status, sex, drug treatment, and effects of drugs of abuse. In short, this Core will use animal models of HIV-infection to provide noninvasive imaging indicators of altered neuronal function and neurotoxicity, and investigate the biochemical mechanisms of these functional abnormalities in collaboration with the Omics Core. Potential biomarkers of altered function can then be tested in humans in the Imaging Core using advanced structural and functional imaging in collaboration with the Developmental Core. Conversely, as functional deficits are detected in human studies, regions identified as demonstrating abnormal neuronal function can be targeted for more thorough investigation in animal studies to (1) replicate the findings using similar imaging methodologies in a better controlled model (e.g., without lifestyle issues) and (2) investigate the cellular and biochemical source(s) of these functional abnormalities in collaboration with the Omics Core and the Cell, Tissue, and Animal Core. These studies will provide new diagnostic capabilities, uncover the biochemical and functional deficits associated with HAND, and allow monitoring of the effects of new therapies on brain biochemistry and function in animals and humans.